Cross-protection induced by highly conserved human B, CD4+, and CD8+ T-cell epitopes-based vaccine against severe infection, disease, and death caused by multiple SARS-CoV-2 variants of concern
BackgroundThe coronavirus disease 2019 (COVID-19) pandemic has created one of the largest global health crises in almost a century. Although the current rate of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections has decreased significantly, the long-term outlook of COVID-19 rema...
| Main Authors: | , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2024-01-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1328905/full |
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| author | Swayam Prakash Nisha R. Dhanushkodi Latifa Zayou Izabela Coimbra Ibraim Afshana Quadiri Pierre Gregoire Coulon Delia F. Tifrea Berfin Suzer Amin Mohammed Shaik Amruth Chilukuri Robert A. Edwards Mahmoud Singer Hawa Vahed Anthony B. Nesburn Baruch D. Kuppermann Jeffrey B. Ulmer Daniel Gil Trevor M. Jones Lbachir BenMohamed Lbachir BenMohamed Lbachir BenMohamed Lbachir BenMohamed |
| author_facet | Swayam Prakash Nisha R. Dhanushkodi Latifa Zayou Izabela Coimbra Ibraim Afshana Quadiri Pierre Gregoire Coulon Delia F. Tifrea Berfin Suzer Amin Mohammed Shaik Amruth Chilukuri Robert A. Edwards Mahmoud Singer Hawa Vahed Anthony B. Nesburn Baruch D. Kuppermann Jeffrey B. Ulmer Daniel Gil Trevor M. Jones Lbachir BenMohamed Lbachir BenMohamed Lbachir BenMohamed Lbachir BenMohamed |
| author_sort | Swayam Prakash |
| collection | DOAJ |
| description | BackgroundThe coronavirus disease 2019 (COVID-19) pandemic has created one of the largest global health crises in almost a century. Although the current rate of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections has decreased significantly, the long-term outlook of COVID-19 remains a serious cause of morbidity and mortality worldwide, with the mortality rate still substantially surpassing even that recorded for influenza viruses. The continued emergence of SARS-CoV-2 variants of concern (VOCs), including multiple heavily mutated Omicron sub-variants, has prolonged the COVID-19 pandemic and underscores the urgent need for a next-generation vaccine that will protect from multiple SARS-CoV-2 VOCs.MethodsWe designed a multi-epitope-based coronavirus vaccine that incorporated B, CD4+, and CD8+ T- cell epitopes conserved among all known SARS-CoV-2 VOCs and selectively recognized by CD8+ and CD4+ T-cells from asymptomatic COVID-19 patients irrespective of VOC infection. The safety, immunogenicity, and cross-protective immunity of this pan-variant SARS-CoV-2 vaccine were studied against six VOCs using an innovative triple transgenic h-ACE-2-HLA-A2/DR mouse model.ResultsThe pan-variant SARS-CoV-2 vaccine (i) is safe , (ii) induces high frequencies of lung-resident functional CD8+ and CD4+ TEM and TRM cells , and (iii) provides robust protection against morbidity and virus replication. COVID-19-related lung pathology and death were caused by six SARS-CoV-2 VOCs: Alpha (B.1.1.7), Beta (B.1.351), Gamma or P1 (B.1.1.28.1), Delta (lineage B.1.617.2), and Omicron (B.1.1.529).ConclusionA multi-epitope pan-variant SARS-CoV-2 vaccine bearing conserved human B- and T- cell epitopes from structural and non-structural SARS-CoV-2 antigens induced cross-protective immunity that facilitated virus clearance, and reduced morbidity, COVID-19-related lung pathology, and death caused by multiple SARS-CoV-2 VOCs. |
| first_indexed | 2024-03-08T12:24:47Z |
| format | Article |
| id | doaj.art-f12511c56f1e46ee92427f5132cbf3d9 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-03-08T12:24:47Z |
| publishDate | 2024-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-f12511c56f1e46ee92427f5132cbf3d92024-01-22T12:07:08ZengFrontiers Media S.A.Frontiers in Immunology1664-32242024-01-011510.3389/fimmu.2024.13289051328905Cross-protection induced by highly conserved human B, CD4+, and CD8+ T-cell epitopes-based vaccine against severe infection, disease, and death caused by multiple SARS-CoV-2 variants of concernSwayam Prakash0Nisha R. Dhanushkodi1Latifa Zayou2Izabela Coimbra Ibraim3Afshana Quadiri4Pierre Gregoire Coulon5Delia F. Tifrea6Berfin Suzer7Amin Mohammed Shaik8Amruth Chilukuri9Robert A. Edwards10Mahmoud Singer11Hawa Vahed12Anthony B. Nesburn13Baruch D. Kuppermann14Jeffrey B. Ulmer15Daniel Gil16Trevor M. Jones17Lbachir BenMohamed18Lbachir BenMohamed19Lbachir BenMohamed20Lbachir BenMohamed21Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, University of California Irvine, School of Medicine, Irvine, CA, United StatesLaboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, University of California Irvine, School of Medicine, Irvine, CA, United StatesLaboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, University of California Irvine, School of Medicine, Irvine, CA, United StatesHigh Containment Facility, University of California Irvine, School of Medicine, Irvine, CA, United StatesLaboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, University of California Irvine, School of Medicine, Irvine, CA, United StatesLaboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, University of California Irvine, School of Medicine, Irvine, CA, United StatesDepartment of Pathology and Laboratory Medicine, School of Medicine, the University of California Irvine, Irvine, CA, United StatesLaboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, University of California Irvine, School of Medicine, Irvine, CA, United StatesLaboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, University of California Irvine, School of Medicine, Irvine, CA, United StatesLaboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, University of California Irvine, School of Medicine, Irvine, CA, United StatesDepartment of Pathology and Laboratory Medicine, School of Medicine, the University of California Irvine, Irvine, CA, United StatesLaboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, University of California Irvine, School of Medicine, Irvine, CA, United StatesDepartment of Vaccines and Immunotherapies, TechImmune, LLC, University Lab Partners, Irvine, CA, United StatesLaboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, University of California Irvine, School of Medicine, Irvine, CA, United StatesLaboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, University of California Irvine, School of Medicine, Irvine, CA, United StatesDepartment of Vaccines and Immunotherapies, TechImmune, LLC, University Lab Partners, Irvine, CA, United StatesDepartment of Vaccines and Immunotherapies, TechImmune, LLC, University Lab Partners, Irvine, CA, United StatesDepartment of Vaccines and Immunotherapies, TechImmune, LLC, University Lab Partners, Irvine, CA, United StatesLaboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, University of California Irvine, School of Medicine, Irvine, CA, United StatesDepartment of Vaccines and Immunotherapies, TechImmune, LLC, University Lab Partners, Irvine, CA, United StatesDivision of Infectious Diseases and Hospitalist Program, Department of Medicine, School of Medicine, the University of California Irvine, Irvine, CA, United StatesInstitute for Immunology; University of California Irvine, School of Medicine, Irvine, CA, United StatesBackgroundThe coronavirus disease 2019 (COVID-19) pandemic has created one of the largest global health crises in almost a century. Although the current rate of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections has decreased significantly, the long-term outlook of COVID-19 remains a serious cause of morbidity and mortality worldwide, with the mortality rate still substantially surpassing even that recorded for influenza viruses. The continued emergence of SARS-CoV-2 variants of concern (VOCs), including multiple heavily mutated Omicron sub-variants, has prolonged the COVID-19 pandemic and underscores the urgent need for a next-generation vaccine that will protect from multiple SARS-CoV-2 VOCs.MethodsWe designed a multi-epitope-based coronavirus vaccine that incorporated B, CD4+, and CD8+ T- cell epitopes conserved among all known SARS-CoV-2 VOCs and selectively recognized by CD8+ and CD4+ T-cells from asymptomatic COVID-19 patients irrespective of VOC infection. The safety, immunogenicity, and cross-protective immunity of this pan-variant SARS-CoV-2 vaccine were studied against six VOCs using an innovative triple transgenic h-ACE-2-HLA-A2/DR mouse model.ResultsThe pan-variant SARS-CoV-2 vaccine (i) is safe , (ii) induces high frequencies of lung-resident functional CD8+ and CD4+ TEM and TRM cells , and (iii) provides robust protection against morbidity and virus replication. COVID-19-related lung pathology and death were caused by six SARS-CoV-2 VOCs: Alpha (B.1.1.7), Beta (B.1.351), Gamma or P1 (B.1.1.28.1), Delta (lineage B.1.617.2), and Omicron (B.1.1.529).ConclusionA multi-epitope pan-variant SARS-CoV-2 vaccine bearing conserved human B- and T- cell epitopes from structural and non-structural SARS-CoV-2 antigens induced cross-protective immunity that facilitated virus clearance, and reduced morbidity, COVID-19-related lung pathology, and death caused by multiple SARS-CoV-2 VOCs.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1328905/fullSARS-CoV-2SL-CoVsCOVID-19vaccineepitopesantibodies |
| spellingShingle | Swayam Prakash Nisha R. Dhanushkodi Latifa Zayou Izabela Coimbra Ibraim Afshana Quadiri Pierre Gregoire Coulon Delia F. Tifrea Berfin Suzer Amin Mohammed Shaik Amruth Chilukuri Robert A. Edwards Mahmoud Singer Hawa Vahed Anthony B. Nesburn Baruch D. Kuppermann Jeffrey B. Ulmer Daniel Gil Trevor M. Jones Lbachir BenMohamed Lbachir BenMohamed Lbachir BenMohamed Lbachir BenMohamed Cross-protection induced by highly conserved human B, CD4+, and CD8+ T-cell epitopes-based vaccine against severe infection, disease, and death caused by multiple SARS-CoV-2 variants of concern Frontiers in Immunology SARS-CoV-2 SL-CoVs COVID-19 vaccine epitopes antibodies |
| title | Cross-protection induced by highly conserved human B, CD4+, and CD8+ T-cell epitopes-based vaccine against severe infection, disease, and death caused by multiple SARS-CoV-2 variants of concern |
| title_full | Cross-protection induced by highly conserved human B, CD4+, and CD8+ T-cell epitopes-based vaccine against severe infection, disease, and death caused by multiple SARS-CoV-2 variants of concern |
| title_fullStr | Cross-protection induced by highly conserved human B, CD4+, and CD8+ T-cell epitopes-based vaccine against severe infection, disease, and death caused by multiple SARS-CoV-2 variants of concern |
| title_full_unstemmed | Cross-protection induced by highly conserved human B, CD4+, and CD8+ T-cell epitopes-based vaccine against severe infection, disease, and death caused by multiple SARS-CoV-2 variants of concern |
| title_short | Cross-protection induced by highly conserved human B, CD4+, and CD8+ T-cell epitopes-based vaccine against severe infection, disease, and death caused by multiple SARS-CoV-2 variants of concern |
| title_sort | cross protection induced by highly conserved human b cd4 and cd8 t cell epitopes based vaccine against severe infection disease and death caused by multiple sars cov 2 variants of concern |
| topic | SARS-CoV-2 SL-CoVs COVID-19 vaccine epitopes antibodies |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1328905/full |
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